Vaccine

a streptococcus pneumonia and vaccine technology, applied in the field of vaccines, can solve the problems of inadequate th-cells available to provide the necessary help, diminish the immune response, and immunological effects, and achieve the effects of preventing or ameliorating pneumococcal infection, eliciting a protective immune response, and preventing or ameliorating the infection

Inactive Publication Date: 2005-09-29
GLAXOSMITHKLINE BIOLOGICALS SA
View PDF1 Cites 19 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006] In one aspect the present invention is an improved Streptococcus pneumonia vaccine comprising 11 or more polysaccharides from different S. pneumonia serotypes conjugated to 2 or more carrier proteins, where the polysaccharides from serotypes 6B, 19F and 23F are conjugated to a first carrier protein and the remaining serotypes are conjugated to 1 or 2 secondary carrier proteins, and where the secondary carrier protein(s) are different from the first carrier protein. Preferably serotypes 6B and 23F are conjugated to the first carrier protein, and more preferably only serotype 6B is conjugated to the first carrier protein. In a preferred embodiment, one of the secondary carrier protein(s) is H. influenzae protein D. The present invention may further comprise S. pneumonia surface proteins, preferably from the PhtX family, the CbpX family, the CbpX truncate family and Ply.
[0007] In a related aspect, the present invention is an improved method to elicit a protective immune response to infants against S. pneumoniae by administering the polysaccharide conjugate vaccine of the present invention.
[0008] In another related aspect, the present invention is an improved method to elicit a protective immune response, that is, for the prevention or amelioration of pneumococcal infection in the elderly (e.g., pneumonia) and / or in infants (e.g., Otitis media), by administering the polysaccharide conjugated vaccine of the present invention and a S. pneumonia surface protein.

Problems solved by technology

However, there can be issues with repeat administration of polysaccharide-protein conjugates, or the combination of polysaccharide-protein conjugates to form multivalent vaccines.
If the B-cells to the carrier protein predominate, there are not enough Th-cells available to provide the necessary help for the B-cells specific to the polysaccharide.
However, the observed immunological effects have been inconsistent, with the total amount of carrier protein in some instances increasing the immune response, and in other cases diminishing the immune response.
Hence there remain technical difficulties in combining multiple polysaccharide conjugates into a single, efficacious, vaccine formulation.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Vaccine
  • Vaccine
  • Vaccine

Examples

Experimental program
Comparison scheme
Effect test

example 1

Determination of the Polysaccharides to which the Immune Response is Regulated with Age

[0062] Human antibody titers to both pre-immune and post-immunization (2 weeks to 3 months) polysaccharides (unconjugated) were collected either internally or via external sources. FIG. 1 shows the relationship between the immunogenicity of each serotype polysaccharide, as measured by the geometric mean fold-increase in antibody titre (GFI) after polysaccharide immunization, and the mean age of the subjects in the study. The linear correlations of log geometric mean fold increase and age give an indication if the immune response is regulated with age. As shown in FIG. 1, serotypes 6, 14, 19 and 23 are significantly correlated with age (por =0.20).

example 2

General Methodology of Determining Antibody Responses in Various Mammals

[0063] The sera were tested for IgG antibodies to the pneumococcal polysaccharides by an ELISA based on a consensus assay for human sera proposed by the joint CDCAWHO workshops held between 1994 and 1996 (WHO 1996, Plikatis et al J. Clin. Microbiol 38: 2043 (2000)). Briefly, purified capsular polysaccharides from ATCC (Rockville, Md., 20852) were coated at 25 μg / ml in phosphate buffered saline (PBS) on high binding microtitre plates (Nunc Maxisorp) overnight at 4 C. The plates were blocked with 10% fetal calf serum (FCS), 1 hour at 37 C. Serum samples were pre-incubated with the 20 μg / ml cell-wall polysaccharide (Statens Serum Institute, Copenhagen) and 10% FCS at room temperature for 30 minutes to neutralize antibodies to this antigen. A reference serum 89SF (courtesy of Dr. C Frasch, USFDA) was treated in the same fashion, and included on every plate. The samples were then diluted two-fold on the microplate ...

example 3

Effects of Combination of Pneumococcal PS-PD Conjugates on Immunogenicity in Adult Rats

[0076] It has been observed that the combination of vaccines into multivalent formulations can result in the decrease in immunogenicity of one or more components of the vaccine. This has been especially observed for conjugate vaccines, and has been called carrier-induced epitopic suppression. The underlying mechanism for this suppression is not well understood, but it tends to happen at higher dosages of carrier protein.

[0077] An 11-valent pneumococcal conjugate vaccine is an example of combination vaccines. Since the combination of each serotype's conjugate will add to the total amount of protein used to immunize, it is important to determine whether the combination of each conjugate vaccine into a multivalent formulation results in a significant decrease in the immunogenicity of the conjugate.

Protocol:

[0078] Adult rats were immunized with pneumococcal-polysaccharide protein D conjugate vac...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
angleaaaaaaaaaa
volumeaaaaaaaaaa
volumeaaaaaaaaaa
Login to view more

Abstract

The present invention provides an optimal formulation of multiple serotype Streptococcus pneumoniae conjugate vaccines.

Description

FIELD OF THE INVENTION [0001] The present invention relates to an improved Streptococcus pneumonia vaccine. BACKGROUND OF THE INVENTION [0002] Children less than 2 years of age do not mount an immune response to most polysaccharide vaccines, so it has been necessary to render the polysaccharides immunogenic by chemical conjugation to a protein carrier. Coupling the polysaccharide, a T-independent antigen, to a protein, a T-dependent antigen, confers upon the polysaccharide the properties of T dependency including isotype switching, affinity maturation, and memory induction. [0003] However, there can be issues with repeat administration of polysaccharide-protein conjugates, or the combination of polysaccharide-protein conjugates to form multivalent vaccines. For example, it has been reported that a Haemophilis influenzae type b polysaccharide (PRP) vaccine using tetanus toxoid (TT) as the protein carrier was tested in a dosage-range with simultaneous immunization with (free) TT and a...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(United States)
IPC IPC(8): A61KA61K39/09A61K39/00A61K39/116A61K39/385A61P11/00A61P31/04
CPCA61K39/092A61K2039/6068A61K2039/6037A61P11/00A61P31/04A61K39/385A61K39/09
Inventor LAFERRIERE, CRAIGPOOLMAN, JAN
Owner GLAXOSMITHKLINE BIOLOGICALS SA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap